Relapsing/Refractory ALK+ Anaplastic Large cell Lymphoma
Conditions
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I-1. Histologically confirmed evidence of relapsed/refractory ALK+ ALCL. If biopsy could not be performed, relapsed/refractory status should be confirmed by molecular analysis whenever possible (increase of MRD quantitative PCR at 2 consecutive measures qualifying for a significant increase according to the same reference laboratory, with clinical signs and symptoms suggestive of progressing disease). In this case, relapsed/refractory status must be reviewed and confirmed by the international coordinating investigator. I-2. Age at inclusion > 6 months I-3. No washout needed, but patients must have recovered from acute toxic effects of all prior therapy before enrollment into the study. A short course of steroids is allowed at the beginning of Nivolumab if it is clinical indicated I-4. Adequate organ function: - Peripheral absolute neutrophil count (ANC) =750/µL in patients without bone marrow involvement and =500/µL in patients with bone marrow involvement (unsupported) - Platelet count =75,000/µL in patients without bone marrow involvement and 50 000 in patients with bone marrow involvement (unsupported) - Hemoglobin =8.0 g/dL (transfusion is allowed) - Serum creatinine =1.5 x upper limit of normal (ULN) for age - Total bilirubin =1.5 x ULN in patients without liver involvement and 12 years of age) or Lansky Play score (for patients =12 years of age) = 40%. I-6. Able to comply with the scheduled disease management (treatment and follow-up), and with the management of toxicity I-7. Females of childbearing potential must have a negative serum ß-HCG pregnancy test within 24 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 5 months after the last study treatment administration. Sexually active males patients must agree to use condom during the study and for at least 7 months after the last study treatment administration. Acceptable contraception is listed in Appendix 5. I-8. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines. I-9. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. I-10. Patients will prior allogeneic HSCT may be included if clinically indicated (see non-inclusion criteria regarding prior allogeneic HSCT). In this case, study inclusion must be confirmed by the international coordinating investigator. Are the trial subjects under 18? yes Number of subjects for this age range: 43 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: E-1. Patients with prior allogeneic HSCT less than 3 months before study inclusion E-2. Patients with prior allogeneic HSCT and any active graft versus host disease (GVHD) and/or any prior grade 3 or 4 GVHD according to International Bone Marrow Transplant Registry (ITBMR) E-3. Previous organ transplantation E-4. Significant hemophagocytosis in bone marrow, spleen, lymph nodes, or liver must be discussed with the Coordinating Sponsor before inclusion E-5. Presence of any = CTCAE grade 2 treatment-related toxicity with the exception of alopecia, fatigue and peripheral neuropathy. E-6. History or evidence of severe uncontrolled illness that contra-indicates use of an investigational drug, or places the patient at unacceptable risk from treatment complications E-7. History or evidence of severe acute or chronic infection unless fully healed at least four weeks prior to screening E-8. Known human immunodeficiency virus (HIV) infection E-9. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. E-10. History or evidence of any auto-immune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. E-11. Subjects with another pathology requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. E-12. Known hypersensitivity to any component of the products (study drug or ingredients) E-13. Concurrent administration of any other antitumor therapy E-14. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening). E-15. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug E-16. Pregnant or breast-feeding female patient E-17. Patient under guardianship or deprived of his liberty by a judicial or administrative decision, patients under safeguards of justice or incapable of giving its consent, patients undergoing psychiatric care under duress E-18. Participation in another clinical study with an investigational product during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort 1: estimate the efficacy of nivolumab treatment in patients with relapsed/refractory ALK+ ALCL in terms of best objective response within the first 24 weeks Cohort 2: estimate the efficacy of nivolumab treatment as consolidative immunotherapy after CR in patients with relapsed/refractory ALK+ ALCL in terms of progression-free survival ;Secondary Objective: Efficacy: • Cohort 1: estimate the efficacy of nivolumab, in terms of - time to response (CR or PR) to nivolumab treatment - response duration in patients who achieve PR/CR - progression-free survival (PFS) - overall survival (OS) - evolution of Minimal Residual Disease (MRD; quantitative PCR) • Cohort 2: estimate the nivolumab efficacy in terms of - OS in the full Cohort 2 - PFS and OS in the subgroup of Cohort 2 patients having received less than 12 months of ALK inhibitor or brentuximab - evolution of MRD levels by quantitative PCR in patients with positive MRD at inclusion Safety (in cohorts 1 and 2): • Assess the short- and long-term safety of the treatment with nivolumab Biology (in cohorts 1 and 2): • Monitor the systemic immune effects of nivolumab • Study the associations between biomarkers (on tumour cells, microenvironment, blood, and bone marrow) and nivolumab efficacy ;Primary end point(s): Cohort 1: Best objective response rate (CR+PR) Cohort 2: PFS ;Timepoint(s) of evaluation of this end point: Cohort 1: Best objective response rate (CR+PR) within the first 24 weeks Cohort 2: 3-year PFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Cohort 1 • Time between the first dose of treatment and the confirmed CR/PR • Duration of response (CR/PR) • Best objective response rate (CR+PR) • Progression-free survival (PFS) • Overall survival • Minimal Residual Disease blood level at various time-points Cohort 2 • Overall survival • PFS and OS in the subgroup of patients having received less than 12 months of ALK inhibitor or brentuximab • Minimal Residual Disease blood level at various time-points Safety in cohorts 1 and 2: • Acute toxicity (NCI-CTCAE v5) during induction treatment, during maintenance treatment, and one month after the end of treatment • Long-term toxicity Biology in cohorts 1 and 2: • Anti-ALK antibody blood level at various time-points • Biomarkers on tumor and its microenvironment, blood and bone marrow, including PDL1 and PDL2 expression, and tumor infiltrating lymphocytes and leucocytes populations/cytokines, at different time points. ;Timepoint(s) of evaluation of this end point: 5 years | — |
Countries
Denmark, France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactCRA
Gustave Roussy
Outcome results
None listed